Aortocoronary saphenous vein bypass graft (SVG) failure is common and is associated with high morbidity and mortality. We recently demonstrated that: (a) in spite of intensive statin therapy prior coronary bypass graft surgery (CABG) patients have high cardiac risk; (b) >50% of those patients have low high-density lipoprotein cholesterol (HDL-C) levels; and (c) SVGs have large atherosclerotic burden with rapid intermediate lesion progression causing cardiac events. Endothelial progenitor cells (EPCs) are important for stabilizing coronary atherosclerotic lesions and may be of particular importance in the friable, prone to rupture SVG plaques. Niacin raises HDL-C, restores the re-endothelialization capacity of EPCs, and slowed the progression of SVG atherosclerosis in one trial of statin-naove patients. However, it remains unknown whether niacin can prevent progression (or cause regression) of SVG atherosclerosis along with increased mobilization of EPCs in prior CABG patients who receive intensive statin therapy. We hypothesize that in patients with an intermediate SVG lesion receiving intensive statin therapy, extended-release niacin (ER-niacin) will significantly reduce the percent atheroma volume of the SVG lesion and will increase mobilization of peripherally circulating endothelial progenitor cell colony forming units (EPC-CFU/mL) compared to placebo. We propose a phase II, single- center, double-blind trial that will randomize 138 prior CABG patients with an intermediate SVG lesion (30%- 60% angiographic diameter stenosis on clinically-indicated coronary angiography), and HDL-C<60 mg/dL to ER-niacin at a dose of 1500-2000 mg daily or matching placebo for 12 months. All patients will receive a statin with goal low-density lipoprotein cholesterol <70 mg/dL. Coronary angiography, intravascular ultrasonography (IVUS) and near-infrared spectroscopy (NIRS) of the target intermediate SVG lesion will be performed at randomization and after 12 months in each patient, along with exercise stress testing at 1 and 12 months and peripheral blood sampling performed at enrollment and at 1, 3, 6, 9 and 12 months post enrollment. The specific objectives of the proposed study are to determine whether compared to placebo, ER-niacin will result in: (1) reduction of percent atheroma volume (PAV) of the intermediate SVG lesion at 12-month IVUS imaging (primary endpoint); (2) reduction of the target lesion total and normalized total SVG atheroma volume, atheroma volume in the most diseased 10-mm subsegment, atheroma volume in the subsegment with lipid core plaque by near-infrared intracoronary spectroscopy, lipid core burden index as assessed by near-infrared intracoronary spectroscopy, and angiographic failure at 12-month follow-up invasive SVG imaging (secondary endpoints); (3) improved exercise capacity and less ischemia by exercise stress testing from 1 to 12 months; (4) greater increase in EPC-CFU/mL of peripheral blood from baseline to 1, 3, 6, and 12 months post enrollment (secondary endpoint); and (5) reduction of major adverse cardiac events (composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoint). PUBLIC HEALTH RELEVANCE: The Potential Impact on Public Health is the identification of a novel therapy (extended release niacin) that could prevent the failure of saphenous vein bypass grafts in patients with coronary artery disease.